1. Field of the Invention
The present invention belongs to the technical field of intermediate synthesis, specifically relating to a method for synthesizing 25-hydroxy cholesterol.
2. Description of Related Art
25-hydroxy cholesterol is an important raw material for the synthesis of 25-hydroxy vitamin D3. The 25-hydroxy vitamin D3, also known as calcifediol, is the active metabolite of vitamin D3, has a stronger physiological activity, and does not need to go through the liver metabolism. The 25-hydroxy vitamin D3 not only has all functions of the ordinary vitamin D3, but also has the following unique functions: {circle around (1)} vitamin D3 in some human or animals cannot be directly converted into 25-hydroxy vitamin D3 due to liver function disorder. Even if many vitamins D3 are taken, these vitamins D3 cannot be absorbed. Therefore, 25-hydroxy vitamin D3, as an active substance, bypasses the liver transformation and is directly supplied for human or animals for absorption; {circle around (2)} the 25-hydroxy vitamin D3 in animals can promote the bone development of poultry, maximize the bone mineral density, reduce chick mortality, reduce osteoporosis and cage layer fatigue, improve quality of egg shells, reduce the breakage rate of egg shells, increase the hatching rate and prolong the egg production cycle; {circle around (3)} compared with vitamin D3, absorption of the 25-hydroxy vitamin D3 is less affected by intestinal damage; and meanwhile, the content of the 25-hydroxy vitamin D3 in plasma is an indicator indicating the nutritional status of vitamin D3.
The 25-hydroxy cholesterol is more difficult in production technique but the market prospect is good and the potential is great. Prior to the present invention, the 25-hydroxy cholesterol is generally prepared by methods such as (a) oxymercuration reduction (Chin. Chem. Lett., 1992, 3, 409), (b) perhydroxytrifluoroacetone hydroxylation (EP594229) or (c) chromium trioxide/acetic anhydride hydroxylation (J. Chem. Research (S), 1999, 708). The reaction formulas are as follows:

Method (a) uses a 24-dehydrocholesterol derivative as a raw material and uses an extremely toxic Hg reagent, so the operation is unsafe, there are great safety and environmental hazards, the post treatment is troublesome, and Hg is very easy to remain in products and is difficult to remove, the medical standards cannot be reached, and industrialization is difficult.
Method (b) uses a 5,6-dibromo cholesterol derivative as a raw material, and oxidized at the position 25 by perhydroxytrifluoroacetone for preparation, but the trifluoroacetone substance is extremely toxic and may have special toxicity, that is, the substance is teratogenetic, carcinogenic and mutagenic. The method has the disadvantages of high instrument requirements, large operation difficulty, troublesome post treatment, and great safety and environmental hazards.
Method (c) uses a 5,6-dichloro cholesterol derivative as a raw material, oxidized by chromium trioxide, acetic anhydride or trifluoroacetic anhydride and then performs reduction with zinc powder. As the method also uses the heavy metal Cr reagent, the usage amount is too large and post treatment is troublesome, there are great environmental hazards, and industrialization cannot be realized.
Therefore, the development of a method for synthesizing 25-hydroxy cholesterol that is efficient, environmentally friendly and easy for realizing industrialization has high economic and social benefits.